Iron and Manganese-Containing Flavonol 2,4-Dioxygenase Mimics
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that of the Cu(II)-containing flavonol 2,4-dioxygenase from Aspergillus japonicus. On the
basis of earlier kinetic and spectroscopic data it can be said that Mn(II) might be the
preferred cofactor for this enzyme and that the catalytic enzyme mechanism is different
from that of the Aspergillus species. After formation of the flavonoxyl-manganese-
superoxide intermediate, the reaction could proceed via two pathways (Fig. 2, a and b). In
the first pathway (a), the superoxide intermediate reacts with the flavonoxyl radical to form
a lactone intermediate and a hydroxide ion via a Criegee intermediate. A Baeyer-Villiger
rearrangement with alkyl migration would then generate the final products. This is identical
to the mechanism proposed for extradiol catechol dioxygenases. In the second pathway (b),
a 2,4-endoperoxide intermediate is formed and decomposes into the depside and carbon
monoxide, similar to the mechanism proposed for the Aspergillus flavonol 2,4-dioxygenase.
Fig. 2. Proposed mechanism of flavonol 2,4-dioxygenase from B. subtilis (Schaab et al., 2006).
Interestingly, recent investigations of flavonol 2,4-dioxygenase from Streptomyces sp. FLA
expressed in E. coli revealed that this enzyme is most active in the presence of Ni(II), with
the next highest level of activity being found with Co(II). In this case the nonredox role of
the metal center was proposed (Merkens et al., 2008).
Studies on structural and functional models are important in order to elucidate the
mechanism of the enzyme reaction. Extensive studies report on the coordination chemistry
of flavonols with various metal ions. Recent crystallographic studies of flavonolato
complexes of copper(I), copper(II), cobalt(III), and zinc(II) disclosed the coordination mode
of the flavonolate ligand, geometries around the metal ions, and their influence on the
delocalization of -electrons in the flavonolate ligand, but only few examples are known for
iron and manganese-containing systems. The stability of the metal flavonolates above can be